Endogenous and exogenous dopamine depress EPSCs in rat nucleus accumbens in vitro via D-1 receptor activation

1. Whole-cell patch clamp recordings were made from nucleus accumbens neurones in slices of rat ventral forebrain. In the presence of picrotoxin (50 mu M), the amplitude of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive glutamate EPSCs, recorded at holding potentials between -80 and -90 mV, was reversibly reduced by 56 +/- 11% (n = 6) by dopamine (30 mu M). The selective dopamine D-1 receptor agonists SKF 38393 (10 mu M) and SKF 81297A (10 mu M), but not the selective D-2 receptor agonist quinpirole (10 mu M), also reversibly depressed the EPSC by 36-48%. The depression of the EPSC by dopamine was completely blocked by the D-1 receptor antagonist SCH 23390 (1 mu M), whereas the D-2 antagonist (-)-sulpiride (1 mu M) was without effect. 2. EPSCs were reversibly depressed by the dopamine mimetic psychostimulants cocaine (1-20 mu M) and amphetamine (10-30 mu M) by 40 +/- 16 and 62 +/- 9%, respectively, but only in about half of the cells tested (11/23 and 6/13, respectively). Their actions were completely reversed by SCH 23390 (1 mu M), indicating that endogenous dopamine can also depress the EPSC via D-1 receptors. 3. No discernable effects of dopamine, SKF 81297A, SKF 38393, quinpirole, cocaine or amphetamine were observed on membrane conductance or holding current (at holding potentials of -80 to -90 mV), suggesting that the depression of the EPSC was solely due to an action on presynaptic D, receptors. 4. In contrast, agents that elevate intracellular levels of adenosine-3': 5'-cyclic monophosphate (cAMP) (forskolin (1-10 mu M), 3-isobutyl-1-methylxanthine (0.1-1 mM), rolipram (10 mu M), and dibutyryl cAMP (0.5-1 mM)) caused a reversible increase in the EPSC amplitude (by 21-150%). Furthermore, in the presence of forskolin (10 mu M), the ability of dopamine to depress synaptic transmission was unaffected. 5. Together these data suggest that both exogenous dopamine and dopamine released from intrinsic nerve terminals attenuate glutamate receptor-mediated synaptic transmission in the nucleus accumbens by presynaptic D-1 receptor activation. The transduction mechanism underlying this effect does not appear to involve the formation of cAMP.